Pharmacokinetic evaluation of fixed-ratio combination of insulin degludec and liraglutide in the treatment of type 2 diabetes

Introduction: Type 2 diabetes is a complex disease requiring individualized and often multi-faceted treatment plans. Balancing glycemic control with adverse medication side effects can be challenging. Combination therapy of basal insulin and GLP-1 receptor agonist therapy appears to provide a balance between glycemic efficacy, hypoglycemia and weight gain.

Areas covered: Available pharmacokinetic data, clinical trials and abstracts regarding fixed-ratio combination of insulin degludec and liraglutide were reviewed. Literature was searched from PubMed and available abstracts using the search term IDegLira up to June 2016.

Expert opinion: Fixed-ratio combination of insulin degludec and liraglutide is associated with sustained glucose-lowering effects as assessed by HbA1c reduction. Overall, hypoglycemia is reduced and weight loss is observed compared to basal insulin alone. There is no significant increase in gastrointestinal side-effects, including nausea compared to non-glucagon-like peptide-1 receptor agonists. Pen injector delivery and dose-step titration allow for individualized therapy intensification. Combined treatment for type 2 diabetes with degludec and liraglutide therapy provides complementary therapeutic efficacy in the treatment of individuals with type 2 diabetes.     

Efficacy and safety of fixed-ratio combination of insulin degludec and liraglutide (IDegLira) for the treatment of type 2 diabetes

Introduction: Type 2 diabetes (T2D) is a progressive disease with increasing prevalence in most countries. The majority of patients with T2D have inadequate glycaemic control, which increases the risk of diabetic complications later in life. New therapies with improved safety profiles are required to tackle the progressive nature of T2D.

Areas covered: The efficacy and safety profile of IDegLira – a once-daily, fixed-ratio combination of insulin degludec and liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), for the treatment of T2D – has been extensively evaluated. IDegLira’s phase 3 clinical trial programme builds upon the clinical programmes of its mono-components, and their cardiovascular outcomes trials. The results are described here, focusing on different patient populations and compared with alternative insulin regimens.

Expert opinion: IDegLira provides superior glycaemic control and mitigates the primary adverse effects associated with insulin therapy (weight gain and hypoglycaemia) and GLP-1RAs (gastrointestinal side effects) with no indication of additive effects. Accordingly, co-formulations such as IDegLira are likely to be increasingly preferred over stepwise addition and titration of the individual agents in the management of T2D.     

Rationale for a titratable fixed-ratio co-formulation of a basal insulin analog and a glucagon-like peptide 1 receptor agonist in patients with type 2 diabetes

Objective: Achieving and maintaining recommended glycemic targets, including those for glycated hemoglobin A1c (A1C), is key to improving outcomes in patients with type 2 diabetes (T2D). As fasting plasma glucose and postprandial glucose contribute to overall A1C, targeting both is essential for sustaining glycemic control.

Methods: This review examines the complementary mechanisms of action of glucagon-like peptide 1 (GLP-1) receptor agonists and basal insulin; they both enhance glucose-stimulated insulin release and suppress glucagon secretion. GLP-1 receptor agonists also slow gastric emptying and increase satiety.

Results: Adding a GLP-1 receptor agonist to therapy with a basal insulin analog has been associated with improved overall glycemic control, with comparable risk of hypoglycemia and no weight gain. Titratable fixed-ratio co-formulations of basal insulin and a GLP-1 receptor agonist have been shown to improve glycemic control, with less complex dosing schedules, possibly increasing treatment adherence. The slow titration of fixed-ratio co-formulations has been shown to reduce the occurrence and severity of gastrointestinal adverse events associated with the use of a separate GLP-1 receptor agonist. Titratable fixed-ratio co-formulations also mitigate insulin-associated weight gain, and show a comparable risk of hypoglycemia to basal insulin use alone.

Conclusions: The efficacy and safety of titratable fixed-ratio co-formulations have been demonstrated for insulin degludec/liraglutide and insulin glargine/lixisenatide in the DUAL and LixiLan trials, respectively, in both insulin-naive and -experienced patients. Titratable fixed-ratio co-formulations represent an attractive treatment option for many patients with T2D.     

Can a fixed-ratio combination of insulin degludec and liraglutide help Type 2 diabetes patients to optimize glycemic control across the day?

‘IDegLira’ combines insulin degludec (IDeg) with the glucagon-like peptide-1 analog liraglutide (Lira) at a ratio of 1 unit IDeg to 0.036 mg Lira. The two components have complementary therapeutic actions for the treatment of Type 2 diabetes. Studies have shown that combinations of basal insulin with glucagon-like peptide-1 receptor agonists can be clinically successful, lowering elevated blood glucose with a low risk of hypoglycemia and weight gain. IDegLira is being assessed in a series of studies (two already published), which provide insights into its clinical utility in previously insulin-naive patients and those failing to achieve good glycemic control on a basal-only insulin regimen. This article critically examines the available data to assess the product’s likely clinical profile.     

The novel use of GLP-1 analogue and insulin combination in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global public health problem. Due to the progressive nature of the disease, a combination(s) of two or more drugs acting on different pathophysiological process is often necessary to achieve early and sustained achievement of individualized glycemic targets. At the same time, choosing the safest option to avoid hypoglycemia is of paramount importance. GLP-1 analogues are a relatively recent class of anti-diabetic drugs, and are highly effective with an acceptable safety profile. Attempts have been made to combine GLP-1 analogues with basal insulin for management of T2DM. Presently GLP-1 analogues like exenatide/long acting exenatide and liraglutide have been co-administered with basal insulin like glargine and detemir respectively, and are approved by regulatory agencies. Currently a fixed dose combination (FDC) of insulin degludec and liraglutide is under development. GLP-1 analogue and insulin as FDC or by co-administration, is a rational method of controlling fasting and postprandial glucose effectively. The efficacy and safety of this combination has been studied in a wide population with promising outcomes. Innovative use of GLP-1 analogues beyond diabetes is also being attempted, and a variety of patents are filed or granted for the same. This review summarizes the current status of GLP-1 and insulin combination in the management of T2DM and highlights the new frontiers in research involving GLP-1. Patents on combination of GLP-1 and insulin which were granted earlier, and the ones which have been applied for, are also discussed.     

The design and discovery of lixisenatide for the treatment of type 2 diabetes mellitus

Introduction: Lixisenatide is a once-daily short-acting glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) used in the treatment of type 2 diabetes mellitus (T2DM). It is used in combination with oral antidiabetics and/or basal insulin in patients inadequately controlled on these medications and who are undergoing diet and lifestyle modification. GLP-1RAs glucose-dependently increase insulin secretion, decrease glucagon secretion, and slow gastric emptying, thereby improving glycemic control. GLP-1RAs are associated with body weight benefits and low rates of hypoglycemia which are welcome in patients with T2DM.

Areas covered: The authors describe the identification of GLP-1RAs as suitable targets for modification with structure-inducing probe technology to improve stability and resistance to proteolytic degradation. Clinical studies have assessed lixisenatide across > 5000 patients as a monotherapy or add-on to a variety of commonly used antidiabetic medications. These studies highlighted the effects of lixisenatide on gastric emptying, explaining its particular improvements in postprandial plasma glucose (PPG) excursions and underscoring its efficacy in combination with insulin glargine. Lixisenatide was well tolerated, with nausea and vomiting being the most frequently reported adverse events.

Expert opinion: The once-daily administration of lixisenatide as well as its substantial sustained effect on gastric emptying and, hence, PPG excursions are all important features compared with the other GLP-1RAs. The combination of two injectables, such as basal insulin to lower fasting plasma glucose and a GLP-1RA that curtails PPG excursions, is clinically valuable and could differentiate lixisenatide from other GLP-1RAs, especially from those continuously acting GLP-1RAs with little effect on gastric emptying and PPG excursions.     

Patient-reported outcomes from a randomized,crossover trial comparing a pen injector with insulin degludec versus a pen injector with insulin glargine U100 in patients with type 2 diabetes

Objective: Type 2 diabetes (T2D) is associated with insulin resistance and deteriorated glycemic control that can be restored with insulin injections. Choice of insulin pen injector may affect complexity, adherence, efficacy of treatment and health-related quality of life. We describe detailed patient-reported outcomes (PROs) on treatment impact and preference comparing insulin degludec (degludec) using FlexTouch¹ versus insulin glargine U100 (glargine U100) with SoloStar² pen injector.

Methods: In this randomized, multicenter (USA), open-label, crossover, treat-to-target study (NCT01570751), patients with T2D using high-dose insulin (≥81?U/day from vials) were randomized (n?=?145) 1:1 to 16?weeks of degludec U200 (3?mL FlexTouch) followed by 16?weeks of glargine U100 (3?mL SoloStar) or vice versa. PRO questionnaires assessed treatment impact and patient preference of pen injectors.

Results: Significantly more patients (p?<?.01) considered FlexTouch “extremely easy” for learning (62.5 vs. 43.0%), maintaining (63.2 vs. 42.2%) and adjusting the dose (63.2 vs. 44.4%), and significantly more were “very” or “extremely confident” in using the device (60.3 vs. 36.3%) and in its accuracy (50.7 vs. 30.4%) versus SoloStar. Significantly more were “not at all bothered” by device discomfort (74.3 vs. 54.1%), whereas device size (83.8 vs. 80.0%) or public use (69.9 vs. 60.7%) were numerically in favor of FlexTouch. Significantly more patients preferred degludec treatment with FlexTouch (59 vs. 22%), preferred to continue (67 vs. 15%) and recommend (67 vs. 14%) use of FlexTouch compared with SoloStar with glargine U100.

Conclusions: In this randomized, crossover trial, lower treatment impact and higher patient preference were reported for FlexTouch versus SoloStar pen injectors.     

Injection force and dose accuracy of FlexTouch for the delivery of a new basal insulin

Objective: The aim of the paper is to determine the dose accuracy and injection force of FlexTouch (FT) filled with insulin degludec 100 U/ml, insulin degludec 200 U/ml and insulin degludec/insulin aspart 100 U/ml, SoloStar (SS) filled with insulin glargine 100 U/ml and KwikPen (KP) filled with insulin lispro mix 75/25 100 U/ml.

Methods: Dose accuracy was measured at minimum, midpoint and maximum doses (FT 1, 2, 40, 80 and 160 U; SS 1, 40 and 80 U; KP 1, 30 and 60 U). Injection force was measured during the injection of the maximum dose.

Results: All doses delivered from FT were within ISO limits (ISO 11608-1:2012) for degludec 100 U/ml, degludec 200 U/ml and degludec/aspart 100 U/ml, and the pens delivered insulin accurately and consistently at all doses tested. Similarly, all tested doses from KP filled with insulin lispro mix 75/25 100 U/ml were within ISO limits, while some doses from SS filled with insulin glargine 100 U/ml were outside ISO limits. FT had a significantly lower injection force than SS and KP (p < 0.05).

Conclusions: FT filled with insulin degludec and insulin degludec/insulin aspart, delivered insulin accurately and consistently within ISO limitations at all doses tested; similarly, KP delivered insulin within ISO limitations at all doses tested and SS delivered most doses within ISO limitations. The significantly lower injection force of FT compared to SS and KP is an important feature that has the potential to make the injection process easier for people with diabetes.     

Efficacy and safety of a needle-free injector in Chinese patients with type 2 diabetes mellitus treated with basal insulin: a multicentre,prospective, randomised,crossover study

ABSTRACT

Objective: To evaluate the efficacy and safety of a needle-free injector in Chinese patients with type 2 diabetes mellitus treated with basal insulin.

Methods: 62 patients with type 2 diabetes were enrolled in a multicenter, randomised, prospective, open-label, crossover study. All patients received subcutaneous insulin glargine administered by a needle-free injector or a glargine pen for 7 ~ 14 days, and were then crossed over after wash out.

Results: Patients in the insulin needle-free injector (NFI) and glargine pen (GP) groups achieved similar fasting blood glucose control . However, the dosage of insulin required to achieve the target FBG level in the NFI group was lower than in the GP group (16.14 ± 5.13 U/day vs 19.25 ± 6.20 U/day, respectively; p = 0.0046). This difference was more significant in patients who received higher insulin dosages compared with those receiving lower dosages. Use of the needle-free injector was also associated with significantly less pain (p < 0.001) and less fear of injection (p < 0.001) than glargine pens.

Conclusion: The use of a needle-free injector can significantly lower the dosage of insulin required to achieve good glycemic control and reduce topical adverse reactions and the fear of injections as well, which help to improve patient compliance.

Clinical Trial Registration Number KY20172077-1; NCT03420040     

The role of the new basal insulin analogs in addressing unmet clinical needs in people with type 1 and type 2 diabetes

Background: Despite improvements in anti-hyperglycemic therapies, there are many unmet clinical needs that hinder successful glycemic control in people being treated with current basal insulin analogs.

Objective: This paper reviews the unmet needs associated with current basal insulin therapy and describes the most recent basal insulins for the treatment of diabetes.

Methods: PubMed was searched for articles on basal insulin analogs published between 2000 and April 2016.

Results: Although long-acting insulin analogs, such as insulin glargine 100 units/mL and insulin detemir, have come towards approximating physiologic basal insulin levels, limitations such as hypoglycemia and intra- and inter-individual variability are associated with their use resulting in glycemic fluctuations. Some basal insulins lack 24?hour coverage, requiring some patients to split their dose, increasing the number of injections required to maintain glycemic control. Fear of hypoglycemia and the need for additional injections often leads to poor compliance and suboptimal glycemic control. Long-acting insulin analogs, such as insulin glargine 300 units/mL and insulin degludec, have improved upon the shortcomings of the current basal insulin analogs. Improved pharmacodynamic/pharmacokinetic profiles afford lower intra-patient variability and an extended duration of action, providing full and stable 24?hour basal insulin coverage with once daily dosing, and comparable efficacy to insulin glargine with lower rates of hypoglycemia.

Conclusion: The improved pharmacodynamic/pharmacokinetic profiles of new long-acting insulin formulations provide greater glycemic control with once daily dosing. With the growing number of therapeutic choices available, physicians have more scope to individualize patient options for basal insulin therapy.     

Comparison between insulin degludec/liraglutide treatment and insulin glargine/lixisenatide treatment in type 2 diabetes: a systematic review and meta-analysis

Aim: To evaluate the efficacy and adverse effects of IDegLira and IGlarLixi treatment and to perform a comparison between two strategies.

Methods: The registration number is CRD42017053952. Randomized controlled trials of IGlarLixi treatment or IDegLira treatment compared with placebo or active hypoglycemic agents in type 2 diabetes were included.

Results: Eight trials were included. The absolute HbA1c change relative to baseline after IGlarLixi treatment was ?1.50% with significance (95% CI, ?1.89% to ?1.12%, p < 0.01); the absolute HbA1c change after IDegLira treatment was ?1.89% with significance (95% CI, ?2.04% to ?1.73%, p < 0.01). Comparisons between IGlarLixi treatment and IDegLira treatment indicated no significant differences between groups. The absolute weight change after IGlarLixi treatment significantly decreased (weighted mean difference (WMD), ?0.62 kg; 95% CI, ?0.93 to ?0.31 kg, p = < 0.01), but the absolute weight change after IDegLira treatment was not significantly changed (WMD, ?0.81 kg; 95% CI, ?3.26 to 1.65 kg, p = 0.52). There were no significant differences between groups.

Conclusion: Glucose control of IGlarLixi treatment or IDegLira treatment was significantly lower than that at baseline. Comparisons between the two treatment groups indicated no significant differences between groups in absolute HbA1c changes or body weight changes relative to baseline.     

Medium-Term Effects of Insulin Degludec on Patients with Type?1 Diabetes Mellitus

Objective

The aim of this study was to analyze the changes in daily blood glucose fluctuation and insulin dose in patients with type 1 diabetes mellitus (T1DM) undergoing basal-bolus therapy following a switching of basal insulin used from insulin glargine or detemir to insulin degludec.

Methods

Seven patients with T1DM were enrolled. All patients treated with insulin glargine or detemir twice daily were switched to insulin degludec with 80–90 % of the prior insulin dose. During the study period, the basal insulin doses were adjusted by the attending physician. The patients underwent continuous glucose monitoring before, 3 days after, and 24 weeks after switching to insulin degludec. The daily insulin dose was analyzed before, 3 days after, and 24 weeks after switching. Glycated hemoglobin levels were measured before and 24 weeks after switching.

Results

The blood glucose profile did not change significantly before and after switching. On the other hand, the total daily insulin dose and total daily basal insulin dose decreased significantly 24 weeks after switching.

Discussion

In patients with T1DM undergoing insulin glargine or detemir treatment, it is possible to achieve similar glycemic control in the medium term with a once daily, lower dose of insulin degludec.     

Lixisenatide as add-on to insulin glargine for the treatment of type 2 diabetes mellitus

Introduction: As type 2 diabetes mellitus (T2DM) advances, patients receiving basal insulin will eventually require another agent on top of their current regimen in order to achieve glycemic control. One such agent that can be administered in combination with basal insulin is the glucagon-like peptide-1 receptor agonist (GLP-1 RA) lixisenatide. GLP-1 RAs, such as lixisenatide, and basal insulin offer complementary mechanisms of action in their ability to provide glycemic control, thus providing a strong rationale for using them in combination with each other for the treatment of T2DM.

Areas covered: The current data available on the use of lixisenatide added to basal insulin for the management of T2DM is reviewed.

Expert opinion: Lixisenatide as add-on to basal insulin provides overall glycemic control as well as offering a number of other treatment benefits, such as a reduction in both body weight and the risk of hypoglycemia. Therefore, when basal insulin becomes inadequate in managing T2DM, lixisenatide should be considered as an add-on agent to help patients achieve glycemic targets with a low risk of hypoglycemic events.     

Long-term efficacy of insulin glargine therapy with an educational programme in type 1 diabetes patients in clinical practice

ABSTRACT

Objective: To investigate the effect of initiating insulin glargine (glargine: LANTUS*), a once-daily basal insulin analogue, plus an educational programme, on glycaemic control and body weight in patients with type 1 diabetes in clinical practice.

Research design and methods: A retrospective analysis of the medical records of 65 patients (mean age: 40.7 ± 13.3 years) with type 1 diabetes was performed. Patients had previously been treated with NPH insulin (NPH; n = 54) or NPH insulin + lente insulin (NPH + lente; n = 11) and then received glargine once daily (bedtime), plus short-acting prandial insulin, for 30 months. Before initiation of glargine, patients participated in a diabetes educational programme and then received physician consultations throughout the study. Metabolic control, body weight and severe hypoglycaemia data were analysed at 9 and 30 months.

Results: Following initiation of glargine, patients showed a decrease in HbA_1c from 7.29 ± 1.1% to 7.06 ± 1.0%; p < 0.01 at 30 months. When the results were analysed by pre-treatment, both NPH-pre-treated and NPH+lente-pre-treated patients showed a significant reduction in HbA_1c of 0.14% and 0.82%, respectively, at 30 months (7.27 ± 1.2% to 7.13 ± 1.1% and 7.42 ± 1.2 to 6.60 ± 0.3%, respectively; p < 0.01). No change in body weight was observed in the overall group. No episodes of severe hypoglycaemia (blood glucose <?40?mg/dL [<?2.2?mmol/L] occurred.

Conclusions: In this retrospective study of medical records, patients with type 1 diabetes treated with insulin glargine over 30 months in combination with educational support and close clinical supervision decreased their HbA_1c levels without weight gain versus previous treatment with NPH insulin or insulin lente. Further studies in a larger cohort of patients would help to confirm these results.     

Insulin and GLP-1 analog combinations in type 2 diabetes mellitus: a critical review

Introduction: Glucagon-like peptide-1 (GLP-1) receptor agonists have been used in clinical management of type 2 diabetes since 2005. Currently approved agents were initially developed and approved for combination therapy with oral antidiabetic drugs (OADs). The potential for combined use with insulin has garnered increasing attention due to the potential to reduce side effects associated with insulin therapy and improve glycemic control.

Areas covered: We reviewed published and other publicly released data from controlled and uncontrolled studies that included subjects treated with insulin/GLP-1 analog combination therapy. The currently available guidance for clinical practice when combining insulin and GLP-1 analogs was also summarized.

Expert opinion: Limited data currently available from placebo-controlled trials support the use of exenatide twice daily or liraglutide once daily in combination with basal insulin and metformin in subjects with type 2 diabetes unable to attain treatment goals. Several randomized controlled trials are currently studying combinations of insulin with various GLP-1 analogs. Additional guidance on the clinical use of these combinations will likely be forthcoming once these studies are reported. Insulin/GLP-1 analog combinations will require optimization of blood glucose monitoring strategies and delivery systems to decrease the risk of administration errors and reduce the potential complexity of these regimens.     

Do glucagon-like peptide-1 receptor (GLP-1R) agonists have potential as adjuncts in the treatment of type 1 diabetes?

ABSTRACT

Introduction: Glucagon-like peptide-1 (GLP-1) is produced by the gut, stimulates insulin secretion from the pancreatic β-cells, and inhibits glucagon secretion from the α-cells. The GLP-1 receptor (GLP-1R) agonists are used in the treatment of type 2 diabetes (T2DM).

Area covered: This review covers the clinical trials of the GLP-1R agonists (exenatide and liraglutide) and their potential as adjunct treatment in type 1 diabetes mellitus (T1DM).

Expert opinion: GLP-1R agonists are unable to increase insulin secretion, in subjects with T1DM, who are C-peptide negative. Also, the GLP-1R agonists either have no effect or cause a small inhibition of glucagon secretion in subjects with T1DM. There is no evidence that the GLP-1R agonists cause a major reduction in HbA1c, or have a major effect on hypo- or hyperglycemia in subjects with TD1M. The main beneficial effect of the GLP-1R agonists is probably the modest weight loss, which may underlie the reduction in dose of insulin used. Given that the GLP-1R agonists cause gastrointestinal adverse effects, and with reduced insulin doses, increase the risk of ketosis, it seems to me that the risk with these agents may outweigh any benefit in T1DM, and that they have little potential as adjuncts in the treatment of T1DM.     

An evaluation of liraglutide including its efficacy and safety for the treatment of obesity

ABSTRACT

Introduction: The prevalence of obesity is increasing worldwide and associated conditions, particularly type 2 diabetes mellitus (T2DM), also show increasing prevalence. Lifestyle intervention should be the first line of management for obesity but additional pharmacotherapy is often required and bariatric surgery is appropriate in more severe cases. Drugs acting as glucagon-like peptide-1 receptor agonists (GLP-1RAs) developed for the management of T2DM reduce body weight and liraglutide is the first GLP-1RA to be approved for the treatment of obesity in patients with and without T2DM.

Areas covered: In this review of relevant published material, the authors summarize the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of liraglutide for the treatment of obesity.

Expert opinion: Liraglutide effectively reduces body weight and body fat through mechanisms involving reduced appetite and lowered energy intake, independent of its glucose-lowering effects. Like most of the other medications currently available for obesity, liraglutide has some common adverse effects, although generally not serious ones. Liraglutide has additional benefits in reducing cardiovascular events in patients with T2DM but the cost and the need for daily injections may limit its use in obesity. Newer GLP-1RAs, such as semaglutide, or other drugs in development for obesity may have advantages over liraglutide.     

Adding prandial GLP-1 receptor agonists to basal insulin: a promising option for type 2 diabetes therapy

Background: Diabetes mellitus is a serious and increasingly prevalent condition in Canada and around the world. Treatment strategies have become increasingly complex, with a widening array of pharmacological agents available for glycemic management in type 2 diabetes mellitus (T2DM). New therapies that act in concert with available basal insulins may represent alternatives to basal insulin intensification with prandial or pre-mixed insulin. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have recently shown promise as useful additions to basal insulin, with significant reductions in glycated hemoglobin and potentially beneficial effects on body weight. This review will focus on pivotal clinical trials to assess the potential benefits of adding prandial GLP-1 RAs to basal insulin in patients with T2DM.

Methods: Clinical studies combining prandial GLP-1 RAs and basal insulin (published between 2011 and July 2017) were identified and reviewed in PubMed, the Cochrane Central Register of Clinical Trials (Issue 6, June 2017), and clinicaltrials.gov.

Results: Most of the studies presented in this review show that the addition of a prandial GLP-1 RA to basal insulin results in equal or slightly superior efficacy compared to the addition of prandial insulin, together with weight loss and less hypoglycemia.

Conclusions: The results of the studies suggest that a prandial GLP-1 RA as an add-on to basal insulin may be a safe and effective treatment intensification option (vs basal-plus or basal-bolus insulin).     

GLP-1 receptor agonists in the treatment of polycystic ovary syndrome

Introduction: Polycystic ovarian syndrome (PCOS) affects many women of child-bearing age and is characterized by hyperandrogenism, ovulatory and metabolic dysfunction. A primary treatment goal is weight reduction. The weight loss effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), previously demonstrated in diabetic and obese non-diabetic patients, offer a unique opportunity to expand the medical options available to PCOS patients.

Areas covered: Available clinical trials of glucagon-like peptide-1 receptor agonist therapy in PCOS were reviewed. Literature was searched from PubMed using appropriate search terms up to November 2016.

Expert commentary: The available studies of GLP-1 RA therapy in the treatment of excess body weight in women with PCOS demonstrate that exenatide and liraglutide are effective in weight reduction either as monotherapy or in combination with metformin. A few studies showed that androgens may be modestly decreased and menstrual frequency may be increased. Eating behavior may be improved with liraglutide therapy. Glucose parameters are generally improved. GLP-1RAs were well-tolerated, with nausea being the most significant adverse side effect. Barriers to utilization may be the short duration studies, lack of familiarity of the medication, the route of administration (injection) and the variable outcomes on ovulation and hyperandrogenism.